Lung tissues damage can be caused by numerous factors such as smoking, aging, air pollution, bacteria, viruses, free radicals, radiation, and chemotherapeutic agents, as well as by hereditary factors. When a lung is damaged, the number of functional alveoli decrease and the alveolar compartments are gradually replaced by fibrotic tissues, causing pulmonary fibrosis. Pulmonary fibrosis is irreversible and causes progressive deterioration in lung functionality. To date, no effective therapy exists for pulmonary fibrosis. Critically, the mortality rate for pulmonary fibrosis is increasing every year.
The lung alveolar epithelium covers the internal surface area of the lung and is composed of two morphological and functional distinct types of cells: type I alveolar epithelial cells (AEC1s) and type II alveolar epithelial cells (AEC2s). When alveoli are injured, AEC2s proliferate and transdifferentiate into AEC1s to repair them facilitate restoration of lung epithelium (1-3). Nevertheless, when severe injuries cause the extensive death of AEC1s, the damaged areas secrete numerous inflammatory cytokines, such as transforming growth factor beta (TGF-β). TGF-β attracts numerous immune cells infiltrating the lesion, which triggers further inflammatory responses. The inflammatory signals enhances the epithelial-mesenchymal transition (EMT) of AEC2s, indicating that numerous AEC2s transform into myofibroblasts. Activated myofibroblasts not only proliferate and express α-smooth muscle actin (α-SMA) but also produce and release the extracellular matrix (ECM). The deposition of ECM components in the interstitial and alveolar space is a hallmark of pulmonary fibrosis. The thickening of alveolar septal walls results in a more severe and irreversible lung consolidation, which impedes the lung's ability to air exchange, leading to a deterioration in pulmonary function (4-10).
Some researchers have studies the effects of stem cells from various origins, such as adipose tissue mesenchymal stem cells (MSCs) (20, 21), bone marrow MSCs (14, 22), and human umbilical mesenchymal stem cells from Wharton's jelly (HUMSCs) (23, 24), in inhibiting inflammatory responses or acute injuries in the lung. However, in most relevant studies, stem cells were transplanted either immediately or one day after lung damage, thus focussing on the effect of stem cells in treating acute injuries or in preventing inflammation in the lung and thus preventing formation of pulmonary fibrosis. Further, it has been reported that bone marrow MSCs injected into the lung immediately after irradiation could differentiate into functional lung cells and thus be useful in treatment of lung injury while those injected at later stage after irradiation would be involved in fibrosis development (25).
In clinical practice, most patients attend clinics for respiratory problems are not in the early stage but usually when pulmonary fibrosis has already developed. There is a need to provide a therapeutically effective approach in treating a fibrosis condition in the lung, particularly reversing the status of pulmonary fibrosis.